Clinicians and clinical researchers engaged in opioid dependence treatment face a clear clinical imperative to improve detoxification strategies in order to avoid the pattern of early relapse and recurrent need for detoxification that characterizes present treatment efforts in this field. While agonist maintenance with methadone or buprenorphine represents the most effective strategy for ensuring long-term treatment retention, opioid replacement therapy is unacceptable to many opioid addicts, particularly those recently diagnosed or the growing proportion of prescription opioid abusers often unwilling to commit to years of opioid maintenance. Efforts to employ a gradual dose reduction of buprenorphine, in a seven- or twenty-eight-day taper, have met with very limited success to date. The addition of naltrexone, a mu opioid receptor antagonist, following buprenorphine taper represents a novel strategy for improving success of the opioid detoxification. In current clinical practice, the requirement for an inpatient detoxification in order to undergo naltrexone induction has constituted a significant barrier to opioid antagonist therapy, because of both patient unacceptability and rising insurance limitations on inpatient treatment. The investigators' extensive experience using antagonist-based treatment of opioid dependence supports the feasibility of implementing an outpatient naltrexone induction procedure. The recently available long-acting injectable formulation of naltrexone, for which FDA approval for opioid dependence is currently being sought, makes this application especially timely. Clear guidelines are needed for the effective induction onto naltrexone following the buprenorphine taper method of opioid detoxification. The proposed investigation will seek to 1) improve long-term outcomes for the buprenorphine taper method of detoxification by adding naltrexone and 2) develop a procedure using buprenorphine and low-dose naltrexone treatment initiation to permit outpatient induction onto long-acting naltrexone. The naltrexone induction regimen proposed in this project is based on previous extensive research conducted in more than 300 patients over the past 12 years by this group of investigators, demonstrating the safety and tolerability of the oral induction strategy in an inpatient setting. In addition, pilot data from the current funding cycle demonstrates the investigators' ability successfully to carry out outpatient naltrexone inductions, leading to long-term retention in treatment and sustained abstinence. Participants seeking opioid detoxification will be randomized to 1) gradual seven-day buprenorphine induction and taper or 2) seven-day buprenorphine with oral naltrexone induction followed by single Vivitrol injection. The primary outcome will be abstinence at Week 5. Secondary outcomes will include successful completion of the seven-day detoxification procedure, abstinence and engagement in treatment through Week 24, mood assessments, and other substance use outcomes. PUBLIC HEALTH RELEVANCE: Current treatment approach for opioid dependence involves a buprenorphine taper method of detoxification; however, relapse rates are as high as 85 percent in the first month after treatment. Opioid agonist maintenance is not an acceptable treatment option for many opioid addicts early in their course of dependence, as well as for newer groups of prescription opioid users. This application seeks to develop and evaluate a novel outpatient opioid detoxification procedure consisting of a buprenorphine/naloxone/Vivitrol induction technique to achieve treatment engagement leading to sustained abstinence.